Nutritional control via Tor signaling in Saccharomyces cerevisiae

Abstract

The yeast Saccharomyces cerevisiae senses and responds to nutrients by adapting its growth rate and undergoing morphogenic transitions to ensure survival. The Tor pathway is a major integrator of nutrient-derived signals that in coordination with other signaling pathways orchestrates cell growth. Recent advances have identified novel Tor kinase substrates and established the protein trafficking membranous network and the nucleus as platforms for Tor signaling. These and other recent findings delineate distinct signaling branches emanating from membrane-associated Tor complexes to control cell growth.

Figure 1. TORC1 dependent signaling events regulating synthesis of ribosome components

A, when nutrients are abundant Tap42 is localized to the membrane and is associated with TORC1. Under these conditions, TORC1 phosphorylates Sch9, which promotes expression of the Ribi and RP genes required for ribosome biogenesis. The RP and Ribi genes are controlled by the localization and activity of specific transactivators (including Abf1, Rap1, Sfp1, Ifh1, Fhl1, Hmo1, and Crf1) as well as the histone acetylase and deacetylase Esa1 and Rpd3, respectively. The precise mechanisms that regulate the activities and localization of these factors, as well as the signaling events that link Sch9 to RP and Ribi promoters, remain to be elucidated. Tor1 translocates to the nucleus in nutrient replete conditions and associates with Pol I and Pol III promoters. B, in response to nutrient deprivation or rapamycin treatment, Sch9 phosphorylation is inhibited and ribosome biogenesis is turned off. Tor1 is exported from the nucleus and Tap42 is displaced from the membrane and, in concert with the catalytic subunits of PP2A (and PP2A-like phosphatases), dephosphorylates specific targets, such as the Pol III repressor Maf1. The signaling events that govern Tor1 nuclear shuttling, and whether these are influenced by the activities of Tap42 or Sch9, are unknown.

Figure 2. Genetic synthetic interaction network of Tor1

A, graphical representation of genes (grouped in functional categories) that when mutated in combination with tor1 result in synthetic lethal or reduced fitness defects. B, schematic representation of the distinct functional categories involved in protein sorting and vacuolar function, that exhibit synthetic interactions with tor1. Mutation of the genes shown in bold confer rapamycin hypersensitivity as demonstrated by two recent studies [46*,47].